The osteoarthritis which occurs in conjunction with canine hip dysplasia resembles the human disease, coxarthrosis. The canine model offers an opportunity to study very early events in the disease process. The disease in dogs is not confined to the hip joints of dysplastic animals as similar changes also occur in the knee and shoulder joints of disease prone subjects. A conspicuous and early change in affected joints is focal degeneration, or fibrillation, of the articular cartilage. The objective of our research is to document events associated with this critical early stage of the disease, and to identify factors which can initiate or modify the process under study. Such factors have recently been identified in synovial fluid and the blood of disease prone dogs. We wish to substantiate these findings, isolate the relevant factor(s), and ascertain their role in the degenerative process. A second but related objective of the proposed research is to substantiate and extend our initial findings in regard to collagen metabolism in focal areas of fibrillated cartilage at an early stage of the disease, before the cartilage as a whole is affected. We are well positioned to examine this aspect of the disease because of the peculiar advantages of the canine model, particularly the spontaneity of the disease, its slow onset, and our capacity to sample cartilage within and surrounding lesions as well as tissue from apparently unaffected joints. The proposed studies would focus on collagen metabolism and accumulation in the matrix of collagen intermediates (notably procollagen) and other, non-collagenous proteins. Our initial efforts in this area would be directed toward substantiation of preliminary evidence that fibronectin is a major constituent of these noncollagenous proteins. This is important, because at present, there is uncertainty in the literature concerning the presence of fibronectin in articular cartilage and its role in arthritic diseases. If these efforts are rewarded we would endeavor to document the role of fibronectin on cartilage collagen metabolism and to ascertain the significance of the accumulation of fibronectin and procolagen in the fibrillated cartilage.